Cardiac contraction in a healthy human heart is initiated by spontaneous excitation of the sinoatrial (“SA”) node, which is located in the right atrium. The electrical impulse generated by the SA node travels to the atrioventricular (“AV”) node where it is transmitted to the bundle of His and to the Purkinje network. The fibers in the Purkinje network branch out in many directions to facilitate coordinated contraction of the left and right ventricles thus providing natural pacing. In some disease states, the heart loses some of its capacity to pace properly. Such dysfunction is commonly treated by implanting a pacemaker.
While effectively improving the lives of many patients, implantable pacemakers rely on a self-contained power source such as a battery and consequently have a limited lifetime before the power source is in need of replacement. Hence, an otherwise healthy patient may require multiple surgeries to replace the power source or the entire implantable pacemaker. In addition, implantable pacemaker batteries are large and are usually the bulkiest pacemaker component. A pacemaker's size and capability for implantation in different body regions are typically dictated by the battery size. Also, implantable pacemakers have very limited or no capacity for directly responding to the body's endogenous signaling the way the SA node responds to such signaling, i.e. by a modulation of the heart rate relative to the physiological and emotional state (e.g. sleep, rest, stress, exercise).
Recently, biological methods of influencing a patient's cardiac cells have been developed, some of which include administering biopharmaceutical compositions that affect cardiac pacing. Developments in genetic engineering have produced methods for genetically modifying cardiac cells to convert non-pacemaking cardiac cells to cardiac cells. For example, U.S. Pat. No. 6,214,620 describes a method for modulating the excitability of ventricular cells by controlling the regulation of the expression of certain ion channels (e.g. K+ channels). PCT Publication No. WO 02/087419 and WO 05/062890A3 describe methods and systems for modulating electrical behavior of cardiac cells by genetic modification of inwardly rectifying K+ channels (IK1) in quiescent ventricular cells. PCT Publication No. WO 02/098286 and WO 05/062958A2 describe methods for regulating pacemaker function of cardiac cells with HCN molecules (HCN 1, 2, 3 or 4 isoforms of the pacemaker current If). It is thought that these and other biological methods and systems may be used as stand-alone cardiac therapies. However, to ensure continuing proper cardiac function, U.S. Publication No. US 2004/0215251 discloses the use of an implantable electrical pacemaker as a backup pacing device, with a biological pacemaker expressing features that regulate the primary pacing functions.
While it is clear from the previously-discussed recent developments that genetic modifications to cardiac cells provide numerous benefits in treating heart arrhythmia, there is also a need for biological pacemakers that function endogenously without requiring genetic modifications. Furthermore, there is a need for the use of autologous biological pacemaker sources to improve the probability for their successful implantation and incorporation in a patient's cardiac tissue with a minimal likelihood for immunorejection to occur.